A Potential Cyclin D2 Expressing Cell Therapy for Heart Regeneration
One of the many frontiers of development in regenerative medicine is the delivery of cells engineered to overexpress one or more specific proteins in order to adjust cell function and activity in a favorable direction. Here, researchers demonstrate that making cardiomyocytes express cyclin D2 before transplantation into an animal model of a heart attack produces beneficial regeneration. The heart is a poorly regenerative organ, and any injury results in scarring and reduced capacity at best. The engineered cardiomyocytes survive following transplantation to some degree, but also produce signaling that provokes greater regeneration activity in native heart cells.
An enduring challenge for bioengineering researchers is the failure of the heart to regenerate muscle tissue after a heart attack has killed part of its muscle wall. That dead tissue can strain the surrounding muscle, leading to a lethal heart enlargement. Heart experts thus have sought to create new tissue - applying a patch of heart muscle cells or injecting heart cells - to replace damaged muscle. Similarly, they have tried to stimulate division of existing heart muscle cells near the damaged area.
After an experimentally induced heart attack in a pig model, heart tissue around the infarction site was injected with about 30 million bioengineered human cardiomyocytes that were differentiated from induced pluripotent stem cells. These cells also overexpress cyclin D2, part of a family of proteins involved in cell division. Compared to control human cardiomyocytes, the cyclin D2-cardiomyocytes showed enhanced potency to repair the heart. They proliferated after injection, and by four weeks, the hearts had less pathogenic enlargement, reduced size of dead muscle tissue and improved heart function.
Intriguingly, the cyclin D2-cardiomyocytes stimulated not only their own proliferation, but also proliferation of existing heart muscle cells around the infarction site of the pig heart, as well as showing angiogenesis, the development of new blood vessels. This ability of the graft cyclin D2-cardiomyocytes to stimulate the proliferation of nearby existing heart cells suggested paracrine signaling, a type of cellular communication where a cell produces a signal that induces changes in nearby cells.